Dual-drug therapy may be the answer to alcohol addiction

August 3, 2021

A drug and anti-drug therapy developed to treat alcohol use disorder (AUD) proved successful in a mouse trial and may even guide substance abuse treatment, so said researchers from the University of California San Francisco (UCSF). The idea is that one potent drug acts on the part of the brain responsible for cravings and habitual behaviour, while its activity elsewhere in the body is blocked by the anti-drug that cannot cross into the brain, thus minimising side effects.

Past studies by Dr. Dorit Ron, a professor of neurology at UCSF, and colleagues point to an enzyme called mTORC1 which helps reinforce memory – including the pleasurable but problematic associations that come with alcohol cravings. Although the activity of mTORC1 can be blocked with the FDA-approved compound rapamycin, people taking it for extended periods often develop side effects such as liver and lung toxicity, sepsis, blood clots, and even a diabetes-like glucose intolerance.

The UCSF team developed one molecule, RapaLink-1, a version of rapamycin that binds to mTORC1 even more tightly; and a second molecule, called Rapablock, administered at precise moments to halt the activity of RapaLink-1 everywhere but in the targeted area of the brain.

In tests, it was observed that mice given both drugs had the best outcomes, reducing their alcohol intake and preference without causing liver toxicity, changing their glucose tolerance or other side effects. RapaLink-1 alone had similar benefits but with adverse effects, while Rapablock on its own was not seen to have any effect, as was expected.

Addiction involves different chemicals such as alcohol, nicotine, cocaine, opiates, and the like – Dr. Ron said the addictive behaviour resulting from each is the same, and could potentially be treated from the same neurological perspective.

Tags: alcohol addiction, drug